Neural influences on sonic hedgehog and apoptosis in the rat penis
Neural influences on sonic hedgehog and apoptosis in the rat penis
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DOI：
10.1095/biolreprod.107.064766
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发表时间：
2008-05-01
影响因子：
3.6
通讯作者：
Podlasek, Carol A.
中科院分区：
文献类型：
--
作者：
Bond, Christopher;Tang, Yi;Podlasek, Carol A.
Sonic Hedgehog(SHH)在维持成年阴茎阴茎海绵体形态中的作用已经确定；然而，SHH本身是如何被调节的机制仍不清楚。由于SHH蛋白的减少是导致阴茎平滑肌细胞凋亡和勃起功能障碍(ED)的原因之一，而SHH治疗可以抑制海绵体神经(CN)损伤诱导的细胞凋亡，因此SHH信号如何调控是一个重要的问题。神经输入可能参与了这一过程，因为两种神经病诱导的ED模型显示阴茎SHH蛋白减少和细胞凋亡增加。我们提出的假设是，海绵体中SHH的丰度受到盆神经节中SHH信号、神经活动或营养因子从盆神经节到海绵体的神经运输的调节。我们已经研究了每一种可能的机制。抑制阴茎中的ShH表明，平滑肌细胞凋亡增加了12倍。抑制盆神经节的SHH可显著增加海绵体的细胞凋亡率(1.3倍)和减少SHH蛋白(1.1倍)。Shh蛋白不通过CN转运。秋水仙碱处理CN后，阴茎中的平滑肌细胞凋亡率显著增加(1.2倍)，SHH蛋白显著减少(1.3倍)。利多卡因处理CN后，阴茎的细胞凋亡率(1.6倍)增加，SHH蛋白减少(1.3倍)。这些结果表明，来自盆神经节/CN的神经活动和营养因子是调节阴茎SHH蛋白和平滑肌丰度所必需的。
The role of sonic hedgehog (SHH) in maintaining corpora cavernosal morphology in the adult penis has been established; however, the mechanism of how SHH itself is regulated remains unclear. Since decreased SHH protein is a cause of smooth muscle apoptosis and erectile dysfunction (ED) in the penis, and SHH treatment can suppress cavernous nerve (CN) injury-induced apoptosis, the question of how SHH signaling Is regulated is significant. It is likely that neural input is involved in this process since two models of neuropathy-induced ED exhibit decreased SHH protein and increased apoptosis in the penis. We propose the hypothesis that SHH abundance in the corpora cavernosa is regulated by SHH signaling in the pelvic ganglia, neural activity, or neural transport of a trophic factor from the pelvic ganglia to the corpora. We have examined each of these potential mechanisms. SHH inhibition in the penis shows a 12-fold increase in smooth muscle apoptosis. SHH inhibition in the pelvic ganglia causes significantly increased apoptosis (1.3-fold) and decreased SHH protein (1.1-fold) in the corpora cavernosa. SHH protein is not transported by the CN. Colchicine treatment of the CN resulted in significantly increased smooth muscle apoptosis (1.2-fold) and decreased SHH protein (1.3-fold) in the penis. Lidocaine treatment of the CN caused a similar increase in apoptosis (1.6-fold) and decrease in SHH protein (1.3-fold) in the penis. These results show that neural activity and a trophic factor from the pelvic ganglia/CN are necessary to regulate SHH protein and smooth muscle abundance in the penis.